Immunoregulatory strategies in corneal transplantation and dry eye disease

Despite substantial advances in our understanding of the cellular and molecular factors that regulate immune homeostasis at the ocular surface and anterior segment, important questions remain. In this thesis I present investigations of two phases of the adaptive immune response – the antigen recognition phase, and the final memory phase. In my experiments I employ murine models of corneal transplantation and dry eye disease. Specifically, I investigate how the activation of antigen-presenting cells is modulated by purinergic signaling and by mesenchymal stem cells in a model of corneal transplantation. Furthermore, I investigate how IL-15 signaling regulates the memory T helper 17 cell pool in age-related dry eye disease. In addition to providing useful models to investigate immunoregulation in the eye, studies of corneal transplantation and dry eye disease are of high translational potential. Corneal transplantation is the most common form of tissue grafting performed worldwide. Despite high success rates in low-risk recipients, failure rates exceed 50% in patients with a history of graft rejection, or with vascularized and inflamed host beds. Dry eye disease is an extremely common chronic condition of the ocular surface, with prevalence estimated to be more than 10% for ages greater than 50 years. Dry eye disease significantly impairs quality of life and is associated with a substantial socioeconomic burden. Accordingly, there is an unmet clinical need for novel therapeutic strategies to improve corneal allograft survival and treat dry eye disease. The data presented in this thesis indicate that both the purinergic receptor antagonist oxidized adenosine triphosphate and mesenchymal stem cell-derived hepatocyte growth factor promote corneal allograft survival by regulating antigen-presenting cell maturation. In addition, the data presented indicate that targeting interleukin-15 signaling is an effective strategy to deplete the memory T helper 17 pool in aged mice and reduce the severity of age-related dry eye disease

"Eyes Closed" and "Eyes Open" Expectations Guide Fixations in Real-World Search

Investigations of search within realistic scenes have identified both bottom-up and top-down influences on performance. Here, I describe two types of top-down expectations that might guide observers looking for objects. Initially, likely locations can be predicted based only on the target identity but without any visual information from the scene (?Eyes closed?). When a visual preview becomes available, a more refined prediction can be made based on scene layout (?Eyes open?). In two experiments participants guessed the location of a target with or without a brief preview of the scene. Responses were consistent between observers and were used to predict the eye movements of new observers in a third experiment. The results confirm that participants use both types of top-down cues during search, and provide a simple method for estimating these expectations in predictive models

Functions of a quiet and un-quiet eye in natural tasks - comment on Vickers

The Quiet Eye (QE) is an interesting phenomenon that has implications for the links between cognition and eye movements as well as for the question of how we examine these links in real world tasks. The gaze behaviour observed in sports and other active tasks is varied in form and function. Although fixation duration has a specific definition in laboratory tasks, in sport and naturalistic actions it is not as easy to interpret. I discuss what we can learn from gaze in natural behaviour and how both quiet and ?un-quiet? eyes may have highly specific functions in different tasks

How the Eyes Tell Lies: Social Gaze During a Preference Task

Social attention is thought to require detecting the eyes of others and following their gaze. To be effective, observers must also be able to infer the person's thoughts and feelings about what he or she is looking at, but this has only rarely been investigated in laboratory studies. In this study, participants' eye movements were recorded while they chose which of four patterns they preferred. New observers were subsequently able to reliably guess the preference response by watching a replay of the fixations. Moreover, when asked to mislead the person guessing, participants changed their looking behavior and guessing success was reduced. In a second experiment, naïve participants could also guess the preference of the original observers but were unable to identify trials which were lies. These results confirm that people can spontaneously use the gaze of others to infer their judgments, but also that these inferences are open to deception

Are fixations in static natural scenes a useful predictor of attention in the real world?

Research investigating scene perception normally involves laboratory experiments using static images. Much has been learned about how observers look at pictures of the real world and the attentional mechanisms underlying this behaviour. However, the use of static, isolated pictures as a proxy for studying everyday attention in real environments has led to the criticism that such experiments are artificial. We report a new study that tests the extent to which the real world can be reduced to simpler laboratory stimuli. We recorded the gaze of participants walking on a university campus with a mobile eye tracker, and then showed static frames from this walk to new participants, in either a random or sequential order. The aim was to compare the gaze of participants walking in the real environment with fixations on pictures of the same scene. The data show that picture order affects interobserver fixation consistency and changes looking patterns. Critically, while fixations on the static images overlapped significantly with the actual real-world eye movements, they did so no more than a model that assumed a general bias to the centre. Remarkably, a model that simply takes into account where the eyes are normally positioned in the head-independent of what is actually in the scene-does far better than any other model. These data reveal that viewing patterns to static scenes are a relatively poor proxy for predicting real world eye movement behaviour, while raising intriguing possibilities for how to best measure attention in everyday life

Goal-driven and bottom-up gaze in an active real-world search task

Mobile eye tracking has become a useful tool in studies of vision and attention in real-world tasks. However, there remains a disconnection between such studies and the laboratory paradigms used by cognitive psychology. In particular, visual search has been studied intensively, but lab search often differs from search in the real world in many respects (e.g., in reality one must walk and move head and eyes to find the target, target and distractors are not equally visible, and objects are frequently occluded). Here, we took a broader view of search behaviour and analyzed the gaze of participants who were asked to walk around within a building, find a room, and then locate a target mailbox. Our aim was to describe the differences in behaviour according to principles of (lab-based) visual search, and we did this by testing the effects of top-down instructions (i.e. having more or less information about where to go) and target saliency (i.e. having a more or less distinctive target to look for). These factors made a difference in a real world context by changing the frequency with which signs and cues in the environment were fixated, and by affecting head and eye movements in the mail-room. Bottom-up saliency had little effect on search time, but our approach revealed how it influenced the coordination of gaze, while still allowing us to make contact with laboratory paradigms

Where have eye been? Observers can recognise their own fixations

We are often not explicitly aware of the location of our spatial attention, despite its influence on our perception and cognition. During a picture memory task, we asked whether people could later recognise their eye fixations in a two-alternative test. In three separate experiments, participants performed above chance when discriminating their own fixation patterns from random locations or locations fixated in a different image. Recognition was much poorer when the task was to spot your own versus someone else?s fixations on the same stimulus, but performance remained better than chance. That we are sensitive to our own scan patterns has implications for perception, memory, and meta-cognition

The impact of facial abnormalities and their spatial position on perception of cuteness and attractiveness of infant faces

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Research has demonstrated that how “cute” an infant is perceived to be has consequences for caregiving. Infants with facial abnormalities receive lower ratings of cuteness, but relatively little is known about how different abnormalities and their location affect these aesthetic judgements. The objective of the current study was to compare the impact of different abnormalities on the perception of infant faces, while controlling for infant identity. In two experiments, adult participants gave ratings of cuteness and attractiveness in response to face images that had been edited to introduce common facial abnormalities. Stimulus faces displayed either a haemangioma (a small, benign birth mark), strabismus (an abnormal alignment of the eyes) or a cleft lip (an abnormal opening in the upper lip). In Experiment 1, haemangioma had less of a detrimental effect on ratings than the more severe abnormalities. In Experiment 2, we manipulated the position of a haemangioma on the face. We found small but robust effects of this position, with abnormalities in the top and on the left of the face receiving lower cuteness ratings. This is consistent with previous research showing that people attend more to the top of the face (particularly the eyes) and to the left hemifield

Age and beauty are in the eye of the beholder

How “old” and “attractive” an individual appears has increasingly become an individual concern leading to the utilisation of various cosmetic surgical procedures aimed at enhancing appearance. Using eyetracking, in the present study we aimed to investigate how individuals perceive age and attractiveness of younger and older faces and what “bottom-up” facial cues are used in this process. One hundred and twenty eight digital images of neutral faces of ages ranging from 20 to 89 years were paired and presented to subjects who judged age and attractiveness levels while having their eye movements recorded. There was an effect of face attractiveness on age-rating accuracy, with attractive faces being rated younger than their true age. Similarly, stimulus age affected attractiveness ratings, with younger faces being perceived as more attractive. Judgments of age and attractiveness were tightly linked to fixations on the eye region, along with the nose and mouth. It is thus likely that cosmetic surgical procedures targeted at the eyes, nose, and mouth may be most efficacious at enhancing one's physical appearance